Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening

被引：79

作者：

Kiss, Robert ^{[1
,2
]}

Kiss, Bela ^{[1
]}

Koenczoel, Arpad ^{[1
]}

Szalai, Ferenc ^{[3
]}

Jelinek, Ivett ^{[4
]}

Laszlo, Valeria ^{[4
]}

Noszal, Bela ^{[2
]}

Falus, Andras ^{[4
]}

Keseru, Gyoergy M. ^{[1
,5
]}

机构：

[1] Gedeon Richter Plc, H-1103 Budapest, Hungary

[2] Semmelweis Univ, Dept Pharmaceut Chem, H-1092 Budapest, Hungary

[3] Natl Informat Infrastruct Inst, H-1132 Budapest, Hungary

[4] Semmelweis Univ, Dept Genet Cell Biol & Immunobiol, H-1089 Budapest, Hungary

[5] Budapest Univ Technol & Econ, Dept Gen & Analyt Chem, H-1111 Budapest, Hungary

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 11期

关键词：

D O I：

10.1021/jm7014777

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were tested by radioligand binding assay and 16 of them possessed significant [H-3]histamine displacement. Several novel scaffolds were identified that can be used to develop selective H4 ligands in the future. As far as we know, this is the first SBVS reported on H4R, representing one of the largest virtual screens validated by the biological evaluation of the virtual hits.

引用

页码：3145 / 3153

页数：9

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